Primary Hyperaldosteronism and Loop Diuretics

Primary Hyperaldosteronism

• Primary hyperaldosteronism causes high blood pressure due to increased aldosterone production.
• Aldosterone stimulates the reabsorption of sodium ions and water in the distal convoluted tubules and collecting ducts leading to increased blood volume, ultimately increasing blood pressure.
• Patients with primary hyperaldosteronism would have an excess of sodium and a deficiency in potassium ions due to increased sodium reabsorption and potassium secretion in the collecting duct.
• ACE inhibitors can be used to treat hypertension associated with primary hyperaldosteronism.
• ACE inhibitors block the conversion of angiotensin I to angiotensin II, which is a potent vasoconstrictor.
• By decreasing angiotesin II levels, ACE inhibitors decrease aldosterone secretion, resulting in less sodium and water retention, which lowers blood pressure.

Loop Diuretics

• Loop diuretics inhibit the reabsorption of sodium and chloride ions in the ascending loop of Henle.
• This results in increased sodium concentration in the filtrate, which draws more water into the urine, increasing urine output.

Glomerular Filtration Membrane

• Three pressures operate at the filtration membrane:
  • Glomerular Blood Hydrostatic Pressure (GBHP): pushes water and solutes from the blood into the filtrate, increasing net filtration pressure.
  • Capsular Hydrostatic Pressure (CHP): exerted by fluid in Bowman's capsule, opposing filtration, and decreasing net filtration pressure.
  • Blood Colloid Osmotic Pressure (BCOP): created by proteins in blood plasma, also opposing filtration and decreasing net filtration pressure.
• Severe diarrhea causes dehydration. This lowers GBHP and increases BCOP, reducing the net filtration pressure.
• Decreased net filtration pressure reduces the glomerular filtration rate (GFR), impairing the kidneys' ability to filter waste efficiently.

Gallbladder Function

• The gallbladder stores and concentrates bile produced by the liver between meals.
• During digestion, especially after consuming fatty foods, the gallbladder contracts and releases bile into the small intestine.
• Bile emulsifies fats, breaking them into smaller droplets, aiding in digestion and absorption.
• The release of bile is stimulated by the hormone cholecystokinin (CCK) released from the small intestine in response to fatty food entering the duodenum.

Cholecystectomy

• Cholecystectomy, removal of the gallbladder, minimally compromises digestion because the liver continues to produce bile.
• After a cholecystectomy, bile drips continuously into the small intestine instead of being stored and released in bursts.
• This may lead to bile acid diarrhea as excess bile in the colon draws water into the stool, resulting in loose bowel movements.

### Triglyceride Digestion

• Mechanical digestion of triglycerides starts in the mouth with chewing and continues with churning in the stomach.
• Bile salts in the small intestine emulsify fats into smaller droplets for efficient enzyme action.
• Pancreatic lipase breaks down triglycerides into monoglycerides and free fatty acids.
• These components combine with bile salts to form micelles that transport them to the intestinal lining.
• Inside intestinal cells, monoglycerides and fatty acids are reassembled into triglycerides.
• Triglycerides are packaged into chylomicrons for transport.
• Chylomicrons enter the lymphatic system via lacteals and are delivered to the bloodstream through the thoracic duct.
• In the bloodstream, chylomicrons deliver triglycerides to tissues for energy or storage.

Micturition Reflex

• The detrusor muscle contracts and the internal urethral sphincter relaxes when the parasympathetic nerves are stimulated.
• Detrusor muscle contraction applies pressure to the bladder, facilitating urine expulsion.
• Urethral sphincter relaxation allows urine to flow from the bladder into the urethra.

### Spinal Cord Injury and Micturition

• Damage to the sympathetic nerves in the L2-L5 region can disrupt the micturition reflex.
• This may lead to urinary retention as the detrusor muscle fails to contract effectively.
• It can also result in urinary incontinence if the sphincter relaxes involuntarily.

Auto-regulation of GFR

• One mechanism that contributes to the regulation of GFR is hormone regulation, specifically, the release of atrial natriuretic peptide (ANP).
• ANP is secreted when the atria stretch, which increases GFR.
• ANP causes relaxation of mesangial cells in the glomerulus, increasing the capillary surface area for filtration.

### Accessory Organs and Digestion

• Salivary glands produce saliva containing amylase to begin carbohydrate digestion in the mouth.
• The liver produces bile, which emulsifies fats in the small intestine.
• The gallbladder stores and concentrates bile from the liver, releasing it into the small intestine for fat digestion.
• The pancreas secretes pancreatic enzymes (lipase, amylase, proteases) and bicarbonate into the small intestine for the digestion of fats, carbohydrates, proteins, and neutralizing stomach acid.

Gastric Secretion

• The stomach contents must be acidic (pH 1.5-3.5) to activate pepsinogen into pepsin, which is essential for protein digestion.
• The acidic environment also kills bacteria and pathogens ingested with food.
• The stomach protects itself from digestion by secreting a thick mucus layer and bicarbonate ions.
• The mucus layer acts as a physical barrier, preventing acid from damaging the epithelial cells.
• Bicarbonate neutralizes acid near the mucosal surface, maintaining a pH-safe environment for the tissue.